Role Of The KLF9 In The Progression Of Pancreatic Ductal Adenocarcinoma

Objective:Pancreatic ductal adenocarcinoma(PDAC)in human being is the one of the most frequently diagnosed cancer worldwide.Human Krüppel-like factor(KLF9)gene has been implicated in mediating a diverse range of biological processes.The role of the KLF9 is uncovered in PDAC.Methods:We evaluated the expression of KLF9 in pancreatic tumor tissue and matched normal samples used IHC,western blot,RT-PCR;overexpression or RNAi knockdown of KLF9 in pancreatic cancer cell lines was used to detect the effect of KLF9 on cell proliferation.Report gene was used to screen the possible action signal pathway of KLF9;Promoter mutation and deletion test was used to confirme the binding site of KLF9.The effect of KLF9 on the tumorigenesis of pancreatic cancer cells was detected in nude mice.Results:Expression of KLF9 effectively forced expression or knockdown with RNAi in pancreatic cancer lines were determined in cell growth and xneograft.In this study,we confirmed that the expression of KLF9 was lower in pancreatic ductal adenocarcinoma tissue compared to normal tissue.Upon KLF9 overexpression,the aggressive behaviors were reduced by obliterating interlinking pathobiological events such as reversing the epithelial to mesenchymal transition(EMT),blocking the expression of stem-cell-like traits.In contrast,silencing the expression of KLF9 augmented EMT and stemness features in relatively less aggressive Bx PC3 pancreatic cancer cells.Furthermore,we identified a KLF9-binding site(BTE)in the promoter region of Frizzled-5,which is a receptor of Wnt/β-catenin signaling,and found that Frizzled-5 was a transcriptional target of KLF9.Using a xenograft model we demonstrated that KLF9 silencing in Bx PC3 cells reverses the stemness features and tumor initiating potency of these cells.Conclusions:Taken together,our findings demonstrated that KLF9 inhibited pancreatic cancer by suppressing the Frizzled-5,a plasma ligand of Wnt/β-catenin signaling and acted as tumor suppressor in PDAC.